Management of emboli has been a prominent issue within the context of the development of new surgical procedures for the last several decades. It is axiomatic that downstream embolus generation constitutes a major drawback within the context of any surgical procedure having a relationship with major organs or organ systems perfused by vessels, wherein diseases or disease states are managed. Minimally invasive techniques have only heightened ongoing awareness of these issues.
There are about 550,000 new strokes in the United States each year. In 1995, stroke mortality was 26.7 per 100,000, or 157,991 deaths. The average cost of care for a patient up to 90 days after a stroke exceeds $15,000. For 10% of patients, the cost of care for the first 90 days after a stroke exceeds $35,000.
A stroke occurs when the nutritive blood flow to part of the brain is suddenly interrupted or when a blood vessel in the brain bursts, spilling blood into the spaces surrounding the brain cells. In the same way that a person suffering a loss of blood flow to the heart is said to be having a heart attack, a person with a loss of blood flow to the brain or sudden bleeding into the brain is said to be having a stroke. Brain cells die when they no longer receive oxygen and nutrients from blood, or when they are damaged by sudden bleeding into or around the brain. Ischemia is the term used to describe the loss of oxygen and nutrients for brain cells when there is inadequate blood flow. Ischemia ultimately leads to infarction, the death of brain cells which are eventually replaced by a fluid-filled cavity, or infarct, in the injured brain.
There are two forms of stroke: hemorrhagic (bleeding into or around the brain), and ischemic (blockage of a blood vessel supplying the brain). Ischemic stroke, in turn, is predominantly associated with three mechanisms: thrombosis of the internal carotid artery: flow-related ischemic events; and cerebral embolism.
Cerebral embolism from the carotid artery lesion is the single most common cause of cerebral ischemic events. Embolism from the atherosclerotic plaque may occur in one of three ways. First, the irregular surface of the plaque is thrombogenic and can accumulate platelet aggregates. If these platelet aggregates become large and embolize to an important cerebral branch, symptoms result. Second, as the atherosclerotic plaque becomes more advanced, it may undergo central degeneration. When this occurs, the plaque may rupture spontaneously, discharging its contents into the lumen of the blood vessel, with subsequent embolism. Third, direct physical trauma to an atherosclerotic plaque or thrombus, as during a carotid endarterectomy operation, may dislodge particulate matter that can embolize to the brain. Regardless of mechanism, the final common pathway of cerebral emboli is mechanical obstruction to nutritive blood flow. The term emboli describes the particles, usually microscopic, that arise from or enter the bloodstream and produce tissue ischemia by lodging within sub-arterial tributaries and depriving tissues of oxygen. Emboli can take the form of blood clots, debris from atherosclerotic plaque, tissue debris from surgery, or air bubbles.
While the layperson is generally aware that atherosclerosis can eventually lead to blood clots that cause heart attacks and stroke, it is also the case that certain medical procedures can provoke emboli and adverse consequences such as stroke and necrosis of tissues distant from the site of formation of the emboli. For example, procedures used in cardiac surgery, such as aortic cannulation, aortic cross-clamping, and proximal coronary artery anastamosis, can disrupt an existing atherosclerotic lesion, provoking emboli taking the form of pieces of the lesion, with consequent stroke. Moreover, these same procedures can provoke the generation blood clots, with the consequent emboli. Emboli that are gas bubbles can arise from medical devices used during cardiopulmonary bypass surgery (Hogue, et al. (2008) Crit. Care Clin. 24:83-89; Falk (2010) European Heart J. 31:278-280). Neurologic complications that are directly linked to embolisms arise during cardiac surgery, where these include transient ischemic attacks, stroke, delirium, coma, and memory deficit (Christenson, et al. (2005) Texas Heart Inst. J. 32:515-521).
Without intending any limitation, the invention provides neurologic embodiments, which include methods for preventing or mitigating stroke, preventing or mitigating transient ischemic attack, preventing or mitigating neurocognitive deficit, and mitigating Alzheimer's disease. Postoperative neurocognitive deficit, which arises from cerebral microemboli, at least in part, can involve impairment of memory, concentration, and language (Gao, et al. (2005) Chest 128:3664-3670, U.S. Pat. No. 7,442,383 issued to Franks, et al; U.S. Pat. Publ. No. 20100173789 of Dambinova). Each of these documents is incorporated herein by reference, as if fully set forth herein. As stated by Gao, et al, neuroprotective therapy “interventions are quite limit.” Accordingly, the present invention provides method for preventing or mitigating stroke, neurocognitive deficit, Alzheimer's disease, optionally with the method of administering a neuroprotecting agent, such as a anti-inflammatory agent. Neuroprotecting agents of the present invention encompass aprotinin, heparin coating of cardiopulmonary bypass (CPB) circuits, barbiturates, xenon gas, and steroids (Gao, et al. (2005) Chest 128:3664-3670).
Additionally, cardiac operations, aortic operations, and aortic instrumentation result in high risk for an embolism or emboli that have pathological consequences on organs other than the brain. For example, cardiac surgery can result in acute renal failure, attributed to embolisms of atherosclerotic material to the kidneys (Davila-Roman, et al. (1999) J. Thorac. Cardiovasc. Surg. 117:111-116). Cardiac surgery can result in pulmonary embolisms (Goldhaber and Schoepf (2004) Circulation 109:2712-2715). Cardiac surgery can also result in pathological embolisms to the extremities (Frank and Velden (2011) New Engl. J. Med. 364:265). Aortic instrumentation encompasses wires, aortic angiography, and a delivery system for a stent graft.
Renal embodiments are provided. Abdominal aortic aneurysms cause about 6000 deaths per year in England and Wales (Symons and Gibbs (2009) Br. J. Hosp. Med. (Lond.) 70:566-571). An abdominal aortic aneurysm (AAA) can treated using an stent, where the stent is sometimes known as a “triple A stent.” Stents used for treating AAA are disclosed (see, e.g., Goncalves, et al. (2010) J. Cardiovasc. Surg. (Torino) 51:515-531; Mastracci (2010) Perspect. Vasc. Surg. Endovasc. Ther. 22:214-218; Choong, et al. (2010) Surgeon 8:28-38). With placement of the stent in the thoracic aorta, and the top end of the stent can be situated somewhat above the renal artery, and the bottom end of the stent can be situated somewhat just beyond the lower surface of the aneurysm, with the body of the stent extending through the entire aneurysm. The installation of the stent, and related mechanical or surgical procedures, can produce emboli, where the emboli can enter the renal artery and, once in the renal artery, travel to the kidneys and cause renal damage. The method of the present invention occludes the renal vein, thereby causing a venoarterial reflex that contracts part of the renal artery, thereby directing emboli away from the kidneys, and instead down the abdominal aorta and towards the legs. The renal embodiment of the inventive method optionally encompasses at least one filter, at least one anticoagulant or thrombolytic agent, the surgery that installs the stent, and any medical procedure for diagnosing the aneurysm. In another aspect, the renal embodiment of the method does not encompass the surgery that installs the stent, or does not include any medical procedure for diagnosing the aneurysm. See, for example, U.S. Pat. No. 6,558,405, issued to McInnes which is incorporated by reference herein in its entirety.
Devices are available for protecting against embolisms, particularly filters and/or baskets, however such devices have only highlighted or underscored the amount of thrombus present in any given procedures. Further, it is noted that where these include balloon occlusion devices and filter devices, intrinsic limitations and the protection has been characterized as being far from complete (Sangiorgi and Columbo (2003) Heart 89:990-992). Inflation of a balloon can be with an air, a fluid such as saline, a gel, and the like. Inflation encompasses partial inflation, optimal inflation, maximal inflation, and complete inflation, unless expressly stated otherwise or dictated otherwise by the context. Deflation encompasses partial deflation or complete deflation, unless expressly stated otherwise, or dictated otherwise by the context.
The present invention takes a new approach by occluding the blood flow in a blood vessel leaving an organ, that is, a vein, where the occlusion re-directs blood entering the organ away from the organ, and where the re-direction takes advantage of the venoarterial reflex. By re-directing the emboli, and by preventing passage of the emboli through the occluded vein, the invention mitigates, extenuates, or in some cases, prevents stroke. Accordingly, there exists a longstanding need to address and manage thrombi. Prior to the instant teachings, a large gap existed.